Recruitment to randomised controlled trials with children

Recruitment to randomised controlled trials is known to be difficult. Poor recruitment has several adverse consequences. It affects the validity of study findings, is a common cause of trial extensions and may result in premature termination of trials, which is a huge loss in terms of invested funds, resources and lost knowledge. Non-completion or delayed completion of studies maintains the uncertainty about the efficacy and safety of interventions, thereby delaying or preventing the use of effective interventions and prolonging the use of ineffective or potentially harmful treatments. Recruitment of children to randomised controlled trials is thought to be more challenging due to the vulnerability of the population and the fact that consent is provided by another person usually parents. This thesis aims to review the recruitment performance, i.e. comparison of achieved to anticipated recruitment, of randomised controlled trials with children and identify the factors associated with good or poor recruitment. We undertook a pilot systematic review of recruitment and retention in randomised controlled trials with children, in published literature, and found that few studies report recruitment information but those that do, report very high rates of percentage total recruitment achieved (%TR) and consent. It was not possible to obtain unbiased estimates of recruitment performance and consent rate due to the likelihood of selective reporting and/or non-publication of trials with unsuccessful recruitment. We subsequently conducted a review of recruitment of children to randomised controlled trials in the National Institute of Health Research (NIHR) Clinical Research Network (CRN) portfolio and found that under-recruitment and delayed recruitment are common problems in paediatric trials. Having a trial manager or coordinator was found to be significantly associated with successful recruitment. Other factors such as being an IMP (Investigational Medicinal Product) vs. non-IMP trial, trial of acute vs. chronic illness, having CTU (Clinical Trials Unit) involvement, pilot/feasibility study and additional trial demands had no statistically significant association with recruitment success. Since recruitment to a clinical trial can be affected by a number of internal and external factors, we conducted a survey with the clinical teams of a multi-centre randomised controlled trial with children, the MAGNETIC trial, to understand the various facilitators and barriers to recruitment. In order to identify the facilitators and barriers to recruitment and establish the recruitment experience of clinical teams in a systematic manner, we developed an evidence based recruitment survey tool. The survey tool is an online questionnaire that presents a comprehensive evidence based list of facilitators and barriers and free text space for responders to record the strategies applied to overcome these barriers and suggestions for change in organisation of trials to boost recruitment. The survey of clinical teams recruiting to the MAGNETIC trial found that a motivated clinical team with effective communication skills, effective coordination between study team members at site and between sites and CTU, trial management support, research experience of PI, presence of a research nurse and availability of a designated research team were imperative for trial recruitment success. Heavy clinical workload, shift patterns of work, lack of trained staff particularly out of hours, GCP training, local clinical arrangements and parental anxiety about the safety of experimental treatment were recognised as important barriers to recruitment. A trial specific barrier was difficulty faced by the clinicians in seeking consent from the parents of an acutely ill child in the emergency setting and suggestions were made for consideration of deferred consent. We concluded that recruitment to randomised controlled trials with children is challenging and poor recruitment and recruitment delays are a common problem. Reporting of recruitment and consent in paediatric trials is poor and needs improvement. Presence of a dedicated trial manager is significantly associated with successful recruitment and the various generic and trial specific facilitators and barriers to recruitment that have been identified can be used by trialists in planning and conducting future clinical trials with children